• Login
    View Item 
    •   DSpace Home
    • Stony Brook University
    • Stony Brook Theses & Dissertations [SBU]
    • View Item
    •   DSpace Home
    • Stony Brook University
    • Stony Brook Theses & Dissertations [SBU]
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsDepartmentThis CollectionBy Issue DateAuthorsTitlesSubjectsDepartment

    My Account

    LoginRegister

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    The Role of Laminin a2 in Oligodendrocyte Development and CNS Myelination

    Thumbnail
    View/Open
    Relucio_grad.sunysb_0771E_10417.pdf (4.610Mb)
    Date
    1-May-11
    Author
    Relucio, Jenne Liza Villaranda
    Publisher
    The Graduate School, Stony Brook University: Stony Brook, NY.
    Metadata
    Show full item record
    Abstract
    The myelin-producing oligodendrocytes of the central nervous system are critical to normal brain function and physiology. The molecular mechanisms that influence oligodendrocyte development and CNS myelination, however, remain poorly understood. One potential factor that may regulate these processes is the extracellular matrix (ECM) molecule laminin. Children with mutations in one type of laminin - the alpha 2 subunit (LAMA2) - have defects in the size and shape of the forebrain and cerebellum, along with white matter abnormalities. However, it is not clear whether laminin a2 modulates oligodendrocytes in vivo, and if so, through which cellular signaling pathways. In this dissertation, I used LAMA2-deficient dy/dy and LAMA2-knockout (dy3k/dy3k) mice to investigate the influence of laminin a2 on oligodendrogenesis, oligodendrocyte maturation, and CNS myelination. We found that laminin a2 regulates the organization and cellular composition of the postnatal subventricular zone (SVZ), a major gliogenic niche. Loss of LAMA2 resulted in abnormal oligodendrogenesis, such that initially LAMA2-knockout mice had fewer oligodendrocyte progenitor cells (OPCs) compared to their wildtype littermates. During the active myelination period, LAMA2-deficient brains were also found to have a developmental delay in oligodendrocyte maturation. These defects in OPC genesis and maturation correlated with axonal dysmyelination in various CNS white matter regions. We also identified several signaling abnormalities that may be contributing to these oligodendrocyte defects. LAMA2-deficient brains showed dysregulated Fyn (a Src Family Kinase known to regulate myelination) and elevated levels of C-terminal Src kinase (Csk) and Csk-binding-protein (Cbp), proteins that suppress Fyn activity. Laminin substrates were furthermore found to modulate Fyn regulation and to promote the transition of cultured oligodendrocyte progenitors to newly-formed oligodendrocytes in a Fyn-dependent manner. These findings indicate that the dysregulation of signaling pathways required for normal oligodendrocyte development may contribute to CNS abnormalities observed in congenital muscular dystrophy type 1A (MDC1A), and identify novel mechanisms by which laminins regulate oligodendrogenesis, oligodendrocyte lineage progression, and CNS myelination in the developing brain.
    URI
    http://hdl.handle.net/1951/56101
    Collections
    • Stony Brook Theses & Dissertations [SBU] [1955]

    SUNY Digital Repository Support
    DSpace software copyright © 2002-2023  DuraSpace
    Contact Us | Send Feedback
    DSpace Express is a service operated by 
    Atmire NV
     

     


    SUNY Digital Repository Support
    DSpace software copyright © 2002-2023  DuraSpace
    Contact Us | Send Feedback
    DSpace Express is a service operated by 
    Atmire NV